The following is offered as background information only and is not admitted to be prior art to the present invention.
Cancer cells are characterized by an ability to proliferate indefinitely and to invade normal tissue cells surrounding a cancerous tumor. In addition, many types of cancer cells can metastasize throughout the body whereby the tumor may be disseminated in the cancer patient's body.
The mechanism of cancer metastasis is presumed as follows: (1) cancer cells proliferate in a primary cancer colony; (2) blood vessels are newly formed; (3) the malignant cancer cells infiltrate and penetrate the newly formed blood vessels; (4) the cancer cells circulate within the human body; (5) the cancer cells reach a target organ; (6) the cancer cells extravasate from blood vessels; (7) the cancer cells proliferate in the target organ; and (8) a metastatic focus is formed.
The cure rate of malignant cancer tumors has increased with early diagnosis and with the progress of therapies, but metastases of malignant tumors are often beyond current therapies. Chemotherapies are used to arrest metastases following removal of tumors but often with unsatisfactory results. It is therefore desirable to develop more effective inhibitors against malignant tumor metastases.
Conventional methods for treating cancer have also increased the survival and quality of life for cancer patients. Such conventional methods include surgery, for example, removal of the prostate gland (radical prostectomy), radiotherapy, and chemotherapy. In addition, bone marrow transplantation is becoming useful in treating patients with certain types of cancers.
Combination therapies may be used in treating cancer and are typically not addictive. In some cases, cross effects and treatment load can result in a lower effectiveness for the combinations, than either treatment alone.
Other treatments such as radiation, while useful for a wide range of cancers, does not typically result in a complete cure. Given the severity of many cancers and the mortality rate, a drug may be thought of as successful if it improves the quality of life by delaying the growth of tumors, or if it prolongs life without actually curing the condition. In many circumstances, an individual is treated with a specific composition or with a combination of therapies that can eliminate from about 90 to about 95% of the malignant cells, but the remaining cells can re-grow and metastasize, ultimately resulting in death.
LIM kinase 1 (LIMK 1) is one of the regulatory proteins that modulate the actin cytoskeleton by inactivating an actin-binding protein, cofilin, through addition of a phosphate group to cofilin. Actin cytoskeleton is maintained by the constant severing and joining of small units of actin and any deviation away from this normal dynamic may lead to abnormal behavior of a particular cell. LIMK1 plays an important role in maintaining cell architecture through actin cytoskeleton. As an important regulator of cell behavior, levels of LIMK1 need to be regulated in cells for the maintenance of normal cellular function. The concentration of LIMK1 has previously been found at increased levels in some cancer cells; for example, cancer cells that are highly aggressive and capable of causing metastasis or the spread of tumors in mice. Research has shown that a partial inhibition of LIMK 1 synthesis using antisense RNA in these cells resulted in the inhibition of cell growth and more specifically, regression of the invasive property of these cells.
Efforts to identify compositions which inhibit the expression of LIMK 1 and, which therefore, should be useful in the treatment and prevention of cancer cell metastasis, has led to the use of the “antisense” or non-encoding LIM Kinase 1, which exhibits an ability to inhibit the expression of LIMK 1 in certain cancer cells.
Antisense RNA mediated gene therapy is a widely used method of gene inactivation and is suitable for gene therapy use. However, RNA mediated gene inactivation does not work for all genes, and may not be used as a global method of gene inactivation.